Pompe disease: Genetics aspects of diagnosis and treatment

Pompe disease (PD) or glycogen storage disease type II (GDGII) (OMIM 232300) is known as a progressiveneuromuscular disorder linked to Glucosidase alpha acid (GAA) gene caused due to absence normal function ofenzyme GAA activity. The clinical phenotype of PD is highly variable and according to the age onset, the diseaseis classified as infantile and late onset PD. GAA is located on chromosome 17q25.1-25.2 and contains 20 exonswith a large number of neutral and pathogenic variations. GAA sequencing is a reliable and feasible tool for goldstandard diagnosis of PD, so study the GAA alterations specially the mutations of GAA subsequently thephenotype- genotype correlation studies are the current studies regard to genetics aspects of PD. Besides theenzyme replacement therapy, gene therapy is candidate as the adjunctive treatment for PD. Gene replacementstrategies offer the potential for long- term expression of a therapeutic protein after a single administration ofvector, and early studies using viral vectors as a delivery system for GAA have yielded promising results. Arecombinant serotype 9 adeno-associated virus (rAAV9) vector carrying a transgene that expresses codonoptimizedhuman acid alpha-glucosidase (hGAA, or GAA) driven by a human desmin (DES) promoter (i.e.,rAAV9-DES-hGAA) has been generated as a clinical candidate vector for Pompe disease. In this review, wehave documented studies are relevant to the GAA alterations regard to genetics diagnosis of PD, also havefocused on the preclinical studies related to gene therapy strategy for PD and its outcomes.

Keywords:

Pompe Disease , Mutation , Gene Therapy , Acid Alpha-Glucosidase